Advances in experimental medicine and biology最新文献

Organisms living in temperate and polar environments encounter seasonal fluctuations that entail changes in temperature, resource availability, and biotic interactions. Thus, adaptations for synchronizing the life cycle with essential resources and persisting through unfavorable conditions are critical. Diapause, a programmed period of developmental arrest and metabolic depression, is widely used by insects to survive winter and synchronize the life cycle. In some cases, insects spend over half the year (or in some cases, multiple years) in a nonfeeding diapause state. Thus, diapause is energetically challenging, and insects accumulate surplus energy stores and/or suppress metabolism to make it through the winter. As the most energy-dense, and often most abundant, energy reserve in insects, lipids play a central role in diapause energetics. In this chapter, we provide an overview of lipid metabolism in the context of diapause. First, as this is the only chapter in this book that covers diapause, we present some of the general features of diapause. We then discuss the role of lipids as an essential energy store during diapause, focusing on patterns of lipid accumulation before diapause and patterns of utilization during diapause. In the next section, we outline some other roles of lipids during diapause in addition to their role as an energy store. Finally, we end the chapter by discussing the molecular regulation of lipid metabolism in diapause, which has received increased attention in recent years.

Insects are the most successful animal group by various ecological and evolutionary metrics, including species count, adaptation diversity, biomass, and environmental influence. This book delves into the underlying reasons behind insects' dominance on Earth. Lipids play pivotal roles in insect biology, serving as fuel for physiological processes, signaling molecules, and structural components of biomembranes and providing waterproofing against dehydration, among other functions. The study of insect flight has been instrumental in advancing our understanding of insect metabolism, with the migratory locust (Locusta migratoria) and the tobacco hornworm (Manduca sexta) serving as prominent models. Throughout the 1980s and 1990s, numerous studies shed light on the role of adipokinetic hormone (AKH), a crucial neuropeptide in lipid mobilization, to support the extraordinary energy demands of insect flight. Remarkably, AKH was the first identified peptide hormone in insects. These pioneering works linking lipids and flight laid the groundwork for subsequent research characterizing the physiological roles of other neuroendocrine factors in energy substrate mobilization across diverse insect species. However, in the omics era, one may be surprised by the limited understanding of the complex cascade of events governing lipid supply to insect flight muscles. Thus, this chapter aims to provide a concise overview of the evolutionary significance of insect flight, emphasizing key advancements that expand our classical knowledge in this field. Ultimately, we hope this chapter serves as a modest tribute to the pioneering researchers of one of the most captivating areas in insect biology, inspiring further exploration into the myriad roles of lipids in insect biology.

Pluripotent stem cells, comprising embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), are characterized by their self-renewal capacity and the ability to differentiate into cells of all three germ layers of an adult animal. Out of the two, iPSCs are generated through the reprogramming of somatic cells by inducing a pluripotency-specific transcriptional program. This process requires a resetting of the somatic cell genome to a pluripotent cell-specific genome, resulting in cellular stress at genomic, epigenetic, and transcriptional levels. Notably, in contrast to the predominant compact and inactive organization of chromatin in somatic cells, the chromatin in ESCs and iPSCs is open. Furthermore, maintaining a pluripotent state needs a plethora of changes in the genetic landscape of the cells. Here, we attempt to elucidate how certain genes safeguard genomic stability in ESCs and iPSCs, aiding in the complex cellular mechanisms that regulate self-renewal, pluripotency, and somatic reprogramming.

Compartmentalization in eukaryotic cells allows the spatiotemporal regulation of biochemical processes, in addition to allowing specific sets of proteins to interact in a regulated as well as stochastic manner. Although membrane-bound organelles are thought to be the key players of cellular compartmentalization, membraneless biomolecular condensates such as stress granules, P bodies, and many others have recently emerged as key players that are also thought to bring order to a highly chaotic environment. Here, we have evaluated the latest studies on biomolecular condensates, specifically focusing on how they interact with membrane-bound organelles and modulate each other's functions. We also highlight the importance of this interaction in neurodegenerative and cardiovascular diseases as well as in cancer.

Three-dimensional (3D) disease modeling and drug screening systems have become important in tissue engineering, drug screening, and development. The newly developed systems support cell and extracellular matrix (ECM) interactions, which are necessary for the formation of the tissue or an accurate model of a disease. Hydrogels are favorable biomaterials due to their properties: biocompatibility, high swelling capacity, tunable viscosity, mechanical properties, and their ability to biomimic the structure and function of ECM. They have been used to model various diseases such as tumors, cancer diseases, neurodegenerative diseases, cardiac diseases, and cardiovascular diseases. Additive manufacturing approaches, such as 3D printing/bioprinting, stereolithography (SLA), selective laser sintering (SLS), and fused deposition modeling (FDM), enable the design of scaffolds with high precision; thus, increasing the accuracy of the disease models. In addition, the aforementioned methodologies improve the design of the hydrogel-based scaffolds, which resemble the complicated structure and intricate microenvironment of tissues or tumors, further advancing the development of therapeutic agents and strategies. Thus, 3D hydrogel-based disease models fabricated through additive manufacturing approaches provide an enhanced 3D microenvironment that empowers personalized medicine toward targeted therapeutics, in accordance with 3D drug screening platforms.

The bone marrow (BM) is a multifactorial, highly dynamic, still not fully "mapped," reservoir. The BM labyrinthine landscape is subject to a relentless debate on the specialized and stem/progenitor cells' scattering within designated microareas. Certainly, BM tissue plays a watchdog role in bone modeling and remodeling, hematopoiesis, immune surveillance, and endocrine response integration. Parameters like tissue topographical distinctiveness, stiffness and porosity grade, and cells' behavioral idiosyncrasies in terms of stem/progenitor cell housing, activation, and motility represent a knotty problem not easily solved. Given that the disruption of BM microdomains has been associated with a number of severe pathological disorders, the comprehension and preservation of the BM workspace at multiple levels have become mandatory. Solid evidence has showed the existence of an intricate and tightly regulated cross-talk between the BM cellular occupants. Direct physical cell-cell connections and soluble mediators, including cytokines, chemokines, growth factors, exosomes and microvesicles, orchestrate composite intracellular signaling routes. The spatiotemporal action of definite biofactors ensures a functional blood-producing organ with a physiological bone turnover and prompts the action of multipotent stromal/hematopoietic cells. Recently, significant research efforts have been addressed to build bioengineered niche-mimic models based on biofunctionalized scaffolds and organoid-like constructs. These artificial BM niches combine and transduce various aspects of bioinformatics and tissue engineering to unravel the complexities of BM organization. This chapter aims to unfold the recent breakthroughs in the understanding of a BM intramural cell-cell dialogue in a physiological and, in some cases, within an inflammatory background. BM maze is gradually being discovered, but there is still a long way to go.

Bone tissue engineering is a promising field that aims to rebuild the bone tissue using biomaterials, cells, and signaling molecules. Materials like natural and synthetic polymers, inorganic materials, and composite materials are used to create scaffolds that mimic the hierarchical microstructure of bone. Stem cells, particularly mesenchymal stem cells (MSCs), play a crucial role in bone tissue engineering by promoting tissue regeneration and modulating the immune response. Growth factors like bone morphogenetic proteins (BMPs), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) are utilized to accelerate bone regeneration. Clinical applications include treating nonunion and mal-union fractures, osteonecrosis, orthopedic surgery, dental applications, and spinal cord injuries. Recent advances in the field include nanotechnology, 3D printing, bioprinting techniques, gene editing technologies, and microfluidic devices for drug testing. However, challenges remain, such as standardization of protocols, large-scale biomaterial production, personalized medicine approaches, cost-effectiveness, and regulatory issues. Current clinical trials are investigating the safety and efficacy of various bone tissue engineering approaches, with the potential to modernize patient care by providing more adequate treatments for bone defects and injuries.

Male factor accounts for 30-50% of infertility cases and may occur due to congenital anomalies or acquired disorders. In such infertility cases where a limited number of mature sperm is produced, a solution is offered to patients with ART applications; however, these methods are inadequate in patients with germ cell aplasia due to damaged microenvironment. Since monolayer cell culture and static culture conditions do not provide the physical conditions of the 3D microenvironment, they have a limited effect on ensuring the execution of in vitro spermatogenesis properly. For this reason, current treatment approaches turn to biomaterial-implemented, microfluidic, and bioreactor systems where 3D physical conditions are provided. This book chapter focuses on static and dynamic culture conditions, as well as the use of biomaterials to increase the success of ex vivo spermatogenesis and microfluidic device-assisted sperm selection in ART.

Contact lenses have become integral tools in the realm of ocular therapeutics, extending beyond their primary function of refractive correction to encompass a diverse array of therapeutic applications. This review explores the evolving role of contact lenses in managing various ocular conditions, highlighting their efficacy in enhancing patient outcomes. Initially developed to correct refractive errors, contact lenses now serve as effective vehicles for delivering medications directly to the ocular surface, offering targeted treatment for conditions such as dry eye syndrome and corneal ulcers. Their ability to provide sustained moisture and facilitate drug absorption makes them indispensable in promoting corneal healing and managing chronic ocular surface diseases. Specialized contact lenses designed for irregular corneas, such as those affected by keratoconus, provide both optical correction and structural support, significantly improving visual acuity and patient comfort. Additionally, orthokeratology lenses have shown promise in controlling myopia progression in children by reshaping the cornea overnight, thereby reducing reliance on corrective eyewear during waking hours. In post-surgical settings, therapeutic contact lenses aid in epithelial regeneration and minimize discomfort, accelerating recovery and improving surgical outcomes. They also play a crucial role in protecting the cornea from external irritants and promoting a stable tear film, crucial for maintaining ocular health. Looking ahead, ongoing advancements in contact lens materials and designs promise further innovation in ocular therapeutics, paving the way for personalized treatment strategies and improved patient care. As such, contact lenses continue to evolve as essential therapeutic tools, offering tailored solutions for a spectrum of ocular conditions and contributing to enhanced quality of life for patients worldwide.

Epigenetic regulation in hematopoietic stem cells (HSCs) research has emerged as a transformative molecular approach that enhances understanding of hematopoiesis and hematological disorders. This chapter investigates the intricate epigenetic mechanisms that control HSCs function, including deoxyribonucleic acid (DNA) methylation, histone modifications, and chromatin remodeling. It also explores the role of non-coding ribonucleic acid (RNAs) as epigenetic regulators, highlighting how changes in gene expression can occur without alterations to the DNA sequence. Epigenetic mechanisms play a pivotal in regulating HSC self-renewal and differentiation, processes essential for maintaining a balanced hematopoietic system in which lineage-specific hematopoietic stem and progenitor cells (HSPCs) pool is sustained. Recent advancements in epigenetic mapping and sequencing technologies have illuminated the dynamic epigenetic landscapes that characterize HSCs and their progeny. Numerous studies have revealed that dysregulation of epigenetic pathways is a hallmark of various hematological malignancies, including leukemias, lymphomas, and myelodysplastic syndromes. This review highlights key findings that demonstrate the impact of epigenetic abnormalities on the disruption of HSPC niches and the progression of oncogenesis in hematological malignancies. Furthermore, this chapter explores the therapeutic potential of targeting epigenetic modifications that are critical in formation and progression of hematologic malignancies. It also discusses the latest developments in epigenetic therapies, including the use of DNA methyltransferase inhibitors, histone deacetylase inhibitors, and emerging drugs targeting other epigenetic regulators. These therapies represent a promising strategy for resetting aberrant epigenetic states, potentially restoring normal hematopoiesis. Conclusively, this chapter offers a thorough overview of the current landscape and future directions of epigenetic research related to the maintenance of the HSPC niches. The insights presented here aim to contribute significantly to the field, offering a reference point for molecular approaches that enhance our understanding of hematopoiesis and its associated hematological malignancies.